A dysfunctional larynx dilemma: Carcinoma recurrence or radiation-induced damage?

@#A 61-year-old male diagnosed with laryngeal squamous cell carcinoma presented with hoarseness, progressive dysphagia leading to aspiration, and dyspnea one month after definitive radiation therapy. Examination revealed a diffusely swollen glottis, paralyzed vocal cords, and post-radiation fibrosis. Several glottic biopsies yielded results negative for malignancy and favored radiation-induced changes. When presented with the option of further diagnostic testing with a positron emission tomography (PET) scan or an outright laryngectomy, the patient decided on the latter. Final histopathologic diagnosis was negative for recurrence of malignancy. This case demonstrates treatment dilemmas for patients with laryngeal carcinoma with uncertain recurrence wherein radical surgical management may prove to be a viable option to achieve both diagnostic certainty and ultimate relief of symptoms.

Otorhinolaryngology Out-Patient Practice in the “Post”-COVID-19 Era: Ensuring a Balance Between Service and Safety

Objective@#To review available resources and provide evidence-based recommendations that may optimize otorhinolaryngologic out-patient health care delivery in the “post”-COVID-19 era while ensuring the safety of our patients, healthcare workers and staff.@*Data Sources@#Relevant peer-reviewed journal articles; task force, organizational and institutional, government and non-government organization recommendations; published guidelines from medical, health-related, and scientific organizations.@*Methods@#A comprehensive review of the literature on the COVID-19 pandemic as it pertained to “post”-COVID 19 out-patient otorhinolaryngologic practice was obtained from peer-reviewed articles, guidelines, recommendations, and statements that were identified through a structured search of the data sources for relevant literature utilizing MEDLINE (through PubMed and PubMed Central PMC), Google (and Google Scholar), HERDIN Plus, the World Health Organization (WHO) Global Health Library, and grey literature including social media (blogs, Twitter, LinkedIn, Facebook). In-patient management (including ORL surgical procedures such as tracheostomy) were excluded. Retrieved material was critically appraised and organized according to five discussion themes: physical office set-up, patient processing, personal protection, procedures, and prevention and health-promotion.@*Conclusion@#These recommendations are consistent with the best available evidence to date, and are globally acceptable while being locally applicable. They address the concerns of otorhinolaryngologists and related specialists about resuming office practice during the “post”-COVID-19 period when strict quarantines are gradually lifted and a transition to the “new” normal is made despite the unavailability of a specific vaccine for SARS-CoV-2. While they target practice settings in the Philippines, they should be useful to ENT (ear, nose & throat) surgeons in other countries in ensuring a balance between service and safety as we continue to serve our patients during these challenging times.

A dysfunctional Larynx dilemma: Carcinoma recurrence or radiation-induced damage?

@#A 61-year-old male diagnosed with laryngeal squamous cell carcinoma presented with hoarseness, progressive dysphagia leading to aspiration, and dyspnea one month after definitive radiation therapy. Examination revealed a diffusely swollen glottis, paralyzed vocal cords, and post-radiation fibrosis. Several glottic biopsies yielded results negative for malignancy and favored radiation-induced changes. When presented with the option of further diagnostic testing with a positron emission tomography (PET) scan or an outright laryngectomy, the patient decided on the latter. Final histopathologic diagnosis was negative for recurrence of malignancy. This case demonstrates treatment dilemmas for patients with laryngeal carcinoma with uncertain recurrence wherein radical surgical management may prove to be a viable option to achieve both diagnostic certainty and ultimate relief of symptoms.

Evaluation of diagnostic accuracy of cervical palpation, contrast enhanced multi-detector computed tomography, and intraoperative macroscopic nodal assessment of cervical lymph node metastasis of head and neck squamous cell carcinoma in Filipinos: A preliminary study

OBJECTIVES: 1) To determine if there is an association between physical examination by cervical palpation, pre-operative contrast-enhanced multi-detector computed tomography (MDCT), and intraoperative lymph node assessment, with final histopathology in the evaluation of cervical lymph node metastasis in Filipino patients with squamous cell carcinoma of the head and neck. 2) To determine the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and likelihood ratios of cervical palpation, contrast enhanced MDCT, and intra-operative lymph node assessment compared with final histopathology in the evaluation of cervical lymph node metastasis in Filipino patients with squamous cell carcinoma of the head and neck.METHODS: Study Design. Retrospective; Cross-sectional. Setting. Tertiary Government Hospital Charity Section, Department of Otorhinolaryngology, Department of Radiology, Department of Pathology. Participants, Patients or Population. Retrospective chart review of all biopsy proven head and neck squamous cell carcinoma patients admitted at the charity ward of a Otorhinolaryngology Department from 2008-2010 who had documented admission physical examination, a pre-operative contrast enhanced multi-detector computed tomography (MDCT) scan of the neck done in the same institution within 20 days or less from date of surgery, and underwent neck dissection with appropriate cervical lymph node level specimen labeling with subsequent post-operative histopathologic evaluation of submitted specimens for neck node metastasis by the Pathology Department of the same institution. After set of exclusion criteria was applied, the analyzed sample included 82 lymph node level samples from 9 patients with head and neck Squamous Cell Carcinoma (SCCA).RESULTS: Pre-operative contrast enhanced MDCT, and intraoperative nodal assessment, were both significantly correlated with the final histopathologic evaluation of neck node metastasis as evaluated with Fisher's Exact test (p = 0.00). Cervical palpation however was not able to show a significant association (p=0.099).Cervical palpation had a sensitivity of 25.00% (8.33-52.59%), specificity of 90.91% (80.61-96.25%), NPV of 83.33 (72.30-90.73%), PPV of 40.00 (13.69-72.63%), accuracy of 78.05%, and a likelihood ratio of 3.33. Pre-operative contrast enhanced MDCT had a sensitivity of 43.75% (20.75-69.45%), specificity of 93.94% (84.44-98.04%), NPV of 87.32 (76.80-93.69%), , PPV of 63.64 (31.61-87.63%), accuracy of 84.15%, and a likelihood ratio of 12.06. Intraoperative surgical evaluation had a sensitivity of 68.75% (41.48-87.87%), specificity of 93.94% (84.44-98.04%), NPV of 92.54 (82.74-97.22%), PPV of 73.33 (44.83-91.09%), accuracy of 89.02%, and a likelihood ratio of 34.10. Further analysis with McNemar's Test comparing MDCT and Intraoperative assessment showed no significant difference (p = 0.387).DISCUSSION AND CONCLUSIONS: In the evaluation of cervical lymph node metastasis for head and neck squamous cell carcinoma in the local setting, the extent of neck dissection, clinical staging and prognosis, as well as adjuvant therapy can be guided by pre-operative contrast enhanced MDCT and intra-operative nodal assessment. Contrast-enhanced MDCT can aid treatment planning in preoperative or non-operative cases; but intraoperative evaluation can be used to guide final extent of surgery. Evaluation solely by physical examination by cervical palpation unfortunately in this study was not able to show a significant association with final histopathology.

Evaluation of diagnostic accuracy of cervical palpation, contrast enhanced multi-detector computed tomography, and intraoperative macroscopic nodal assessment of cervical lymph node metastasis of head and neck squamous cell carcinoma in Filipinos: A preliminary study

@#<p><strong>OBJECTIVES:</strong> 1) To determine if there is an association between physical examination by cervical palpation, pre-operative contrast-enhanced multi-detector computed tomography (MDCT), and intraoperative lymph node assessment, with final histopathology in the evaluation of cervical lymph node metastasis in Filipino patients with squamous cell carcinoma of the head and neck. 2) To determine the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and likelihood ratios of cervical palpation, contrast enhanced MDCT, and intra-operative lymph node assessment compared with final histopathology in the evaluation of cervical lymph node metastasis in Filipino patients with squamous cell carcinoma of the head and neck.</p><p><strong>METHODS:</strong> Study Design. Retrospective; Cross-sectional. Setting. Tertiary Government Hospital Charity Section, Department of Otorhinolaryngology, Department of Radiology, Department of Pathology. Participants, Patients or Population. Retrospective chart review of all biopsy proven head and neck squamous cell carcinoma patients admitted at the charity ward of a Otorhinolaryngology Department from 2008-2010 who had documented admission physical examination, a pre-operative contrast enhanced multi-detector computed tomography (MDCT) scan of the neck done in the same institution within 20 days or less from date of surgery, and underwent neck dissection with appropriate cervical lymph node level specimen labeling with subsequent post-operative histopathologic evaluation of submitted specimens for neck node metastasis by the Pathology Department of the same institution. After set of exclusion criteria was applied, the analyzed sample included 82 lymph node level samples from 9 patients with head and neck Squamous Cell Carcinoma (SCCA).</p><p><strong>RESULTS:</strong> Pre-operative contrast enhanced MDCT, and intraoperative nodal assessment, were both significantly correlated with the final histopathologic evaluation of neck node metastasis as evaluated with Fisher's Exact test (p = 0.00). Cervical palpation however was not able to show a significant association (p=0.099).Cervical palpation had a sensitivity of 25.00% (8.33-52.59%), specificity of 90.91% (80.61-96.25%), NPV of 83.33 (72.30-90.73%), PPV of 40.00 (13.69-72.63%), accuracy of 78.05%, and a likelihood ratio of 3.33. Pre-operative contrast enhanced MDCT had a sensitivity of 43.75% (20.75-69.45%), specificity of 93.94% (84.44-98.04%), NPV of 87.32 (76.80-93.69%), , PPV of 63.64 (31.61-87.63%), accuracy of 84.15%, and a likelihood ratio of 12.06. Intraoperative surgical evaluation had a sensitivity of 68.75% (41.48-87.87%), specificity of 93.94% (84.44-98.04%), NPV of 92.54 (82.74-97.22%), PPV of 73.33 (44.83-91.09%), accuracy of 89.02%, and a likelihood ratio of 34.10. Further analysis with McNemar's Test comparing MDCT and Intraoperative assessment showed no significant difference (p = 0.387).</p><p><strong>DISCUSSION AND CONCLUSIONS:</strong> In the evaluation of cervical lymph node metastasis for head and neck squamous cell carcinoma in the local setting, the extent of neck dissection, clinical staging and prognosis, as well as adjuvant therapy can be guided by pre-operative contrast enhanced MDCT and intra-operative nodal assessment. Contrast-enhanced MDCT can aid treatment planning in preoperative or non-operative cases; but intraoperative evaluation can be used to guide final extent of surgery. Evaluation solely by physical examination by cervical palpation unfortunately in this study was not able to show a significant association with final histopathology.</p>

Isolation and biochemical characterization of bradykinin-potentiating peptides from Bitis gabonica rhinoceros

Background: Venoms represent a still underexplored reservoir of bioactive components that might mitigate or cure diseases in conditions in which conventional therapy is ineffective. The bradykinin-potentiating peptides (BPPs) comprise a class of angiotensin-I converting enzyme (ACE) inhibitors. The BPPs usually consist of oligopeptides with 5 to 13 residues with a high number of proline residues and the tripeptide Ile-Pro-Pro (IPP-tripeptide) in the C-terminus region and have a conserved N-terminal pyroglutamate residue. As a whole, the action of the BPPs on prey and snakebite victims results in the decrease of the blood pressure. The aim of this work was to isolate and characterize novel BPPs from the venom of Bitis gabonica rhinoceros. Methods: The crude venom of B. g. rhinoceros was fractionated by size exclusion chromatography and the peptide fraction (<7 kDa) was separated by reverse phase chromatography (RP-HPLC) and analyzed by ESI-IT-TOF-MS/MS. One new BPP was identified, synthetized and assayed for ACE inhibition and, in vivo, for edema potentiation. Results: Typical BPP signatures were identified in three RP-HPLC fractions. CID fragmentation presented the usual y-ion of the terminal P-P fragment as a predominant signal at m/z 213.1. De novo peptide sequencing identified one Bothrops-like BPP and one new BPP sequence. The new BPP was synthesized and showed poor inhibition over ACE, but displayed significant bradykinin-induced edema potentiation. Conclusions: So far, few BPPs are described in Viperinae, and based on the sequenced peptides, two non-canonical sequences were detected. The possible clinical role of this new peptides remains unclear.(AU)

Isolation and biochemical characterization of bradykinin-potentiating peptides from Bitis gabonica rhinoceros

Abstract Background: Venoms represent a still underexplored reservoir of bioactive components that might mitigate or cure diseases in conditions in which conventional therapy is ineffective. The bradykinin-potentiating peptides (BPPs) comprise a class of angiotensin-I converting enzyme (ACE) inhibitors. The BPPs usually consist of oligopeptides with 5 to 13 residues with a high number of proline residues and the tripeptide Ile-Pro-Pro (IPP-tripeptide) in the C-terminus region and have a conserved N-terminal pyroglutamate residue. As a whole, the action of the BPPs on prey and snakebite victims results in the decrease of the blood pressure. The aim of this work was to isolate and characterize novel BPPs from the venom of Bitis gabonica rhinoceros. Methods: The crude venom of B. g. rhinoceros was fractionated by size exclusion chromatography and the peptide fraction ( 7 kDa) was separated by reverse phase chromatography (RP-HPLC) and analyzed by ESI-IT-TOF-MS/MS. One new BPP was identified, synthetized and assayed for ACE inhibition and, in vivo, for edema potentiation. Results: Typical BPP signatures were identified in three RP-HPLC fractions. CID fragmentation presented the usual y-ion of the terminal P-P fragment as a predominant signal at m/z 213.1. De novo peptide sequencing identified one Bothrops-like BPP and one new BPP sequence. The new BPP was synthesized and showed poor inhibition over ACE, but displayed significant bradykinin-induced edema potentiation. Conclusions: So far, few BPPs are described in Viperinae, and based on the sequenced peptides, two non-canonical sequences were detected. The possible clinical role of this new peptides remains unclear.

Renal failure in a patient with primary antiphospholipid syndrome.

Antiphospholipid antibody syndrome (APLA) is a syndrome complex characterized by recurrent arterial or venous thrombosis, recurrent fetal wastage, thrombocytopenia and presence in serum of antibodies against negatively charged phospholipids like lupus anticoagulant (LA), anticardiolipin antibody (ACLA) and subgroups. These are classified further as primary (wherein this occurs in isolation) and secondary (associated with infection, drugs and malignancies). It is uncommon to find both LA and ACLA in primary APLA syndrome (unlike as in the secondary form). Renal manifestations which include renal arterial and venous occlusion and infarction and thrombotic microangiopathy have also been infrequently described. We hereby present a case of primary APLA syndrome with unusual features of LA and ACLA occurring together and also the presence of renal failure due to left renal artery thrombosis and right renal artery occlusion.

Primary drug resistance to Mycobacterium tuberculosis in renal transplant recipients.

BACKGROUND. After renal transplantation, patients have an up to 5% chance of being infected with Mycobacterium tuberculosis and there are reports from western countries of a 24% mortality if the infection is drug resistant. We investigated primary drug resistance in renal transplant recipients in Vellore, Tamil Nadu. METHODS. Between January 1987 and December 1993 we studied 695 patients (who had received 717 renal allografts) for evidence of tuberculosis, and performed drug sensitivity tests. RESULTS. Forty-three patients had culture-proven infection with Mycobacterium tuberculosis of whom 40 had drug sensitivity tests done. Initial drug resistance was seen from 1991. Rifampicin resistance was seen in 2, 1 and 4 patients and isoniazid resistance in 1, 2 and 2 patients in 1991, 1992 and 1993, respectively of the 23 isolates tested for drug susceptibility. Multi-drug resistance was seen in 1 and 2 patients in 1992 and 1993. CONCLUSIONS. This is probably the first report in India of primary drug resistance of Mycobacterium tuberculosis in renal allograft recipients. It is a cause for concern as it may indicate a large reservoir of drug-resistant patients in the community.